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Jerry Y Niederkorn - One of the best experts on this subject based on the ideXlab platform.

  • role of interferon γ and cytotoxic t lymphocytes in Intraocular Tumor rejection
    Journal of Leukocyte Biology, 2016
    Co-Authors: Ann J Ligocki, Joseph R Brown, Jerry Y Niederkorn
    Abstract:

    The eye is normally an immunosuppressive environment. This condition is better known as immune privilege and protects the eye from immune-mediated inflammation of tissues that cannot regenerate. However, immune privilege creates a dilemma for the eye when Intraocular neoplasms arise. In some cases, immune privilege is suspended, resulting in the immune rejection of Intraocular Tumors. This study employed a mouse model in which interferon-g–dependent Intraocular Tumor rejection occurs. We tested the hypothesis that this rejection requires interferon-g for the generation and functional capacity of cytotoxic T lymphocyte–mediated rejection of Intraocular Tumors. Tumors grew progressively in the eyes of interferon-g knockout mice, even though the mice generated Tumor-specific cytotoxic T lymphocyte responses in the periphery. However, interferon-g knockout mice rejected Tumors that were introduced into extraocular sites. Subcutaneous Tumor immunization before Intraocular challenge led to Tumor rejection and preservation of the eye in wild-type mice. By contrast, Tumors grew progressively in the eyes of interferon-g knockout mice despite their ability to generate peripheral Tumor-specific cytotoxic T lymphocytes as well as the capacity of CD8 + T cells to enter the eye as shown by the presence of CD8 and perforin message and CD3 + CD8 + leukocytes within the Tumor-bearing eye. We found that cytotoxic T lymphocytes generated in wild-type mice and adoptively transferred into interferon-g knockout mice mediated the rejection of Intraocular Tumors in interferon-g knockout hosts. The results indicate that interferon-g is critical for the initial priming and differentiation of cytotoxic T lymphocytes residing in the periphery to produce the most effect antiTumor function within the eye. J. Leukoc. Biol. 99: 000–000; 2016.

  • natural killer t cells contribute to neutrophil recruitment and ocular tissue damage in a model of Intraocular Tumor rejection
    Investigative Ophthalmology & Visual Science, 2016
    Co-Authors: Ann J Ligocki, Jerry Y Niederkorn
    Abstract:

    Purpose Immune privilege of the eye protects the nonregenerative ocular tissues from innate and adaptive immune-mediated inflammation. In the case of Intraocular Tumors, immune privilege can be arrested to allow for immune-mediated rejection. Activation of innate immune cells can contribute to necrosis of the Intraocular Tumor and bystander ocular tissue. Identifying the cellular components of the innate immune system that contribute to ocular destruction, but are not needed for Tumor rejection, provides insights into the immunopathological sequelae in Intraocular Tumor rejection. Methods Wild-type (WT), Jα18 knockout (KO) mice lacking type I natural killer T (NKT) cells, and CD1d KO mice lacking all NKT cells, were used to identify the role of type II NKT cells in Intraocular Tumor rejection immunopathology. Results CD1d KO mice had significantly lowered rates of necrotic eye destruction during Tumor rejection compared to WT or Jα18 KO mice. Transcriptome and protein analyses revealed that CD1d KO mice had significantly lower expression of CXCL3 compared to WT or Jα18 KO mice, and this was associated with decreased neutrophil recruitment. The presence of type II NKT cells in WT or Jα18 KO mice led to increased CXCL3, which attracted neutrophils to the Intraocular Tumor and culminated in destruction of the eye. Conclusions We found that type II NKT cells are critical in initiating a damaging inflammatory antiTumor response involving the recruitment of neutrophils that compromises the integrity of the eye. Loss of type II NKT cells or depleting neutrophils allows for a productive Intraocular Tumor response that converts the rejection phenotype to preserve the eye.

  • ifn γ independent Intraocular Tumor rejection is mediated by a macrophage dependent process that leaves the eye intact
    Journal of Leukocyte Biology, 2012
    Co-Authors: Terry G Coursey, Peter Chen, Jerry Y Niederkorn
    Abstract:

    Intraocular Tumors reside in an immune-privileged site, yet in certain circumstances, they can undergo immune rejection. Ocular Tumor rejection can follow one of two pathways. One pathway is CD4 T cell-dependent and culminates in ischemic necrosis of the Tumor and phthisis (atrophy) of the eye. A second pathway is also CD4 T cell-dependent but does not inflict collateral injury to ocular tissues, and the eye is preserved. We isolated two clones of a murine Tumor, Ad5E1 that undergo profoundly different forms of immune rejection in the eye. Clone 2.1 Tumors undergo an ischemic necrotizing form of rejection that requires IFN-, T cells, and ocular macrophages and culminates in destruction of the eye. By contrast, the second clone of Ad5E1, clone 4, undergoes rejection that also requires T cells and ocular macrophages, but leaves the eye in pristine condition (nonphthisical rejection). Here, we demonstrate that nonphthisical Tumor rejection of clone 4 Tumors is IFN-independent but requires an ocular macrophage population that contains M1 and M2 macrophages. Clone 4 Tumor-bearing eyes displayed ten- and 15-fold increases in M2- and M1-associated markers Arg1 and NO2, respectively. This is in sharp contrast to previous results with clone 2.1 Tumor rejection, in which M2 markers were undetectable, and the eye was destroyed. These results suggest that the presence of M2 macrophages tempers the immune rejection of Intraocular Tumors and promotes immune effectors that inflict minimal injury to innocent bystander cells and thereby preserve the integrity and function of the eye. J. Leukoc. Biol. 92: 939–950; 2012.

  • cd8 t cells circumvent immune privilege in the eye and mediate Intraocular Tumor rejection by a tnf α dependent mechanism
    Journal of Immunology, 2007
    Co-Authors: Dru S. Dace, Peter Chen, Jerry Y Niederkorn
    Abstract:

    Although Intraocular Tumors reside in an immune-privileged environment, T cells can circumvent immune privilege and mediate Tumor rejection without inducing damage to normal ocular tissue. In this study, we used a well-characterized Tumor, Ad5E1 (adenovirus type 5 early region 1), to analyze the role of CD8+ T cells in the pristine rejection of Intraocular Tumors. It has been previously documented that Ad5E1 Tumor rejection can occur in the absence of CD8+ T cells. However, here we find that CD8+ T cells infiltrated Intraocular Ad5E1 Tumors in C57BL/6 mice. Surprisingly, CD8+ T cells from Tumor-rejector mice could mediate Intraocular Tumor rejection following adoptive transfer to SCID mice. In determining the mechanisms behind CD8+ T cell-mediated Tumor rejection, we discovered that antiTumor CTL activity was neither observed nor necessary for rejection of the Intraocular Tumors. CD8+ T cells from rejector mice did not produce IFN-γ in response to Ad5E1 Tumor Ags or use FasL to mediate Intraocular Tumor rejection. Also, CD8+ T cells did not use perforin or TRAIL, as CD8+ T cells from perforin knockout (KO) and TRAIL KO mice conferred protection to SCID recipient mice following adoptive transfer. We discovered that CD8+ T cells used TNF-α to mediate Tumor rejection, because Ad5E1 Tumor cells were highly sensitive to TNF-α-induced apoptosis and CD8+ T cells from TNF-α KO mice did not protect SCID mice from progressive Ad5E1 Tumor growth. The results indicate that CD8+ T cells circumvent immune privilege and mediate Intraocular Tumor rejection by a TNF-α-dependent manner while leaving the eye intact and vision preserved.

  • ocular immune privilege is circumvented by cd4 t cells leading to the rejection of Intraocular Tumors in an ifn γ dependent manner
    Journal of Leukocyte Biology, 2007
    Co-Authors: Dru S. Dace, Hassan Alizadeh, Peter Chen, Jerry Y Niederkorn
    Abstract:

    Although Intraocular Tumors reside in an immune-privileged site, they can circumvent immune privilege and undergo rejection, which typically follows one of two pathways. One pathway involves CD4(+) T cells, delayed-type hypersensitivity (DTH), and the culmination in ischemic necrosis of the Tumor and phthisis (atrophy) of the eye. The second pathway is DTH-independent and does not inflict collateral injury to ocular tissues, and the eye is preserved. In this study, we used a well-characterized Tumor, Ad5E1, to analyze the role of IFN-gamma in the nonphthisical form of Intraocular Tumor rejection. The results showed that IFN-gamma induced Tumor cell apoptosis, inhibited Tumor cell proliferation, and promoted rejection by inhibiting angiogenesis. Microarray analysis revealed that IFN-gamma induced up-regulation of five antiangiogenic genes and down-regulation of four proangiogenic genes in Ad5E1 Tumor cells. Although IFN-gamma knockout (KO) mice have progressively growing Intraocular Tumors, IFN-gamma was not needed for the elimination of extraocular Tumors, as all IFN-gamma KO mice rejected s.c. Tumor inocula. This represents a heretofore unrecognized role for IFN-gamma in circumventing ocular immune privilege and eliminating Intraocular Tumors. The findings also reveal that some IFN-gamma-independent Tumor rejection processes are excluded from the eye and may represent a new facet of ocular immune privilege.

Rossella Appolloni - One of the best experts on this subject based on the ideXlab platform.

  • adenoma of the non pigmented ciliary epithelium a rare Intraocular Tumor with unusual immunohistochemical findings
    Pathology Research and Practice, 2009
    Co-Authors: Irene Pecorella, Luciano Ciocci, Marina Modesti, Rossella Appolloni
    Abstract:

    A case of adenoma of the non-pigmented ciliary epithelium with smooth muscle differentiation is reported. This uncommon ocular Tumor affected a 36-year-old woman, and had caused decreased visual acuity and a total cataract. Ultrasound biomicroscopy disclosed an associated persistent hyperplasic primary vitreous (PHPV). Sectoral cyclectomy with removal of the mass and intracapsular cataract extraction were performed. The Tumor was diffusely positive for vimentin, smooth muscle actin, NSE, and S-100, focally for CD68 and Melan-A, and was negative for desmin, EMA, HMB-45, and CD99. Occasional cells reacted for cytokeratin. The proliferation index, as assessed by Ki-67, was below 10%. The overlying non-neoplastic ciliary epithelium was positive for vimentin, NSE, and S-100. Myofilaments are not totally unexpected in ciliary adenomas; however, such a diffuse and strong positivity for smooth muscle actin, as in the present case, has only been observed in one case before, but should be considered in the differential diagnosis of these neoplasms.

Carol L. Shields - One of the best experts on this subject based on the ideXlab platform.

  • usefulness of pax8 immunohistochemistry in adult Intraocular Tumor diagnosis
    Ophthalmology, 2020
    Co-Authors: Hardeep Singh Mudhar, Ralph C Eagle, Tatyana Milman, Tracy Sanderson, Leanne Pheasey, Simon M L Paine, Sachin M Salvi, I G Rennie, P A Rundle, Carol L. Shields
    Abstract:

    Purpose To evaluate the distribution of the PAX8 transcription factor protein in ocular tissues and to investigate if immunohistochemical stains for this biomarker are useful in the diagnosis of Intraocular Tumors. Design Observational case series. Participants Excision and cytologic analysis specimens of 6 ciliary body epithelial neoplasms, 2 iris epithelial neoplasms, 3 retinal pigment epithelial neoplasms, 3 Intraocular medulloepitheliomas, 15 uveal melanomas, and 5 uveal melanocytomas. Methods Hematoxylin–eosin and PAX8 immunohistochemical stains were performed on all specimens. In appropriate cases, bleached preparations and other immunohistochemical stains, including AE1/AE3 cytokeratin, Lin28A, and CD45, were performed. Main Outcome Measures Distribution of PAX8 expression in normal and neoplastic tissue. Results Strong nuclear PAX8 expression was observed in the normal corneal epithelium, iris sphincter pupillae muscle, iris pigment epithelium and dilator muscle complex, nonpigmented and pigmented epithelia of the ciliary body, lens epithelium, and a subset of retinal neurons. The normal retinal pigment epithelium and uveal melanocytes did not stain for PAX8. The ciliary body epithelial and neuroepithelial Tumors (adenoma, adenocarcinoma, and medulloepithelioma) showed uniform strong nuclear PAX8 immunoreactivity. All melanocytic Tumors (iris melanoma, ciliary–choroidal melanoma, and melanocytoma) and retinal pigment epithelial neoplasms showed negative results for PAX8. A subset of Tumor-associated lymphocytes, most prominent in uveal melanoma, showed positive results for PAX8. The uniformity of the PAX8 staining was superior to the variable cytokeratin staining in the ciliary epithelial neoplasms and the variable Lin28A staining in malignant medulloepithelioma. The veracity of PAX8 staining was equally as robust on cytologic analysis and open-flap biopsy specimens of ciliary epithelial and iris epithelial neoplasms, melanocytoma, and melanoma. Conclusions PAX8 has proven to be a very useful diagnostic marker in a select group of adult Intraocular Tumors, and we highly recommend its inclusion in diagnostic antibody panels of morphologically challenging Intraocular neoplasms.

  • pearls and pitfalls of intraarterial chemotherapy for retinoblastoma
    Journal of Neurosurgery, 2012
    Co-Authors: Pascal Jabbour, Nohra Chalouhi, Stavropoula Tjoumakaris, Fernando L Gonzalez, Aaron S Dumont, Rohan Chitale, Robert H Rosenwasser, Carlos Bianciotto, Carol L. Shields
    Abstract:

    Retinoblastoma is a deadly eye cancer in children, leading to death in 50%–70% of children in undeveloped nations who are diagnosed with it. This malignancy is the most common Intraocular Tumor in childhood worldwide. The good prognosis in developed nations is related to early detection and advanced treatments. With the advent of intraarterial chemotherapy, neurosurgeons have taken a central role in the treatment of this pediatric condition. Intraarterial chemotherapy is a novel treatment for retinoblastoma whereby chemotherapeutic agents are precisely delivered into the ophthalmic artery, minimizing systemic toxicity. This procedure has shown impressive results and has allowed a dramatic decrease in the rate of enucleation (eye removal) in advanced and refractory retinoblastoma. Recent reports have raised some concerns about the risk of ocular vasculopathy, radiation-related toxicity, and the potential for metastatic disease after intraarterial chemotherapy. In the authors' experience of more than 3 year...

  • Vitreous asteroid hyalosis prolapse into the anterior chamber simulating iris metastasis.
    Middle East African journal of ophthalmology, 2012
    Co-Authors: Carol L. Shields, Massi Romanelli-gobbi, Sara E. Lally, Jerry A. Shields
    Abstract:

    Two asymptomatic elderly women who underwent cataract extraction 7 or more years previously and with Intraocular lens placement presented with a linear bead-like white multinodular mass in the inferior angle simulating iris metastasis versus large inflammatory precipitates. There was no iris infiltration. In the first case, the posterior lens capsule was intact and there was no evidence of gelatinous vitreous in the anterior chamber, whereas in the second case, the capsule was open and there was gelatinous vitreous prolapse. In both cases, there was asteroid hyalosis in the vitreous. Both patients were diagnosed with prolapsed vitreous asteroid hyalosis into the anterior chamber and managed with observation. Vitreous asteroid hyalosis can prolapse into the anterior chamber of pseudophakic elderly patients with or without capsular opening and can simulate an Intraocular Tumor.

  • long term follow up of giant nodular posterior scleritis simulating choroidal melanoma
    Archives of Ophthalmology, 2000
    Co-Authors: Hakan Demirci, Jerry A. Shields, Carol L. Shields, Santosh G Honavar, David S. Bardenstein
    Abstract:

    A 41-year-old asymptomatic woman was referred for enucleation of a 7.5-mm-thick Intraocular Tumor suspected to be choroidal melanoma. The clinical findings combined with imaging studies suggested instead a diagnosis of giant nodular posterior scleritis. A scleral biopsy was performed to confirm the diagnosis. After 12 years of observation, the lesion has remained stable and visual acuity has been preserved. Nodular posterior scleritis can present with no symptoms of pain, redness, or visual disturbance and can remain quiet for many years. It must be clinically differentiated from choroidal melanoma.

David S. Bardenstein - One of the best experts on this subject based on the ideXlab platform.

Ido Didi Fabian - One of the best experts on this subject based on the ideXlab platform.

  • a biological tissue adhesive and dissolvent system for Intraocular Tumor plaque brachytherapy
    Ophthalmic Surgery and Lasers, 2016
    Co-Authors: Ofira Zloto, Vicktoria Vishnevskiadai, Joseph Moisseiev, Michael Belkin, Ido Didi Fabian
    Abstract:

    Purpose To examine a novel technique for simplified placement and removal of plaque brachytherapy by fibrin glue and urokinase (medac Gmbh, Hamburg, Germany). Materials and methods In six enucleated porcine eyes, plaques were placed on the episclera and fibrin glue was applied to cover it. Urokinase was used to dissolve the glue in three eyes and saline was used in three eyes. Adhesion strength was measured further on 15 plaques affixed to porcine eyes (glued in five with intact conjunctiva, glued in five with removed conjunctiva, and sutured in five). Results Saline had no effect on the glue-plaque-eye complex, whereas the urokinase (0.38 mL ± 0.08 mL) easily dissolved the adhesion between the glue layer and surrounding tissues. The weight required to detach the plaques was 0.349 kg ± 0.173 kg for glued eyes with intact conjunctiva, 0.405 kg ± 0.083 kg for sutured eyes (P = .59), and 0.032 kg ± 0.004 kg for glued eyes without intact conjunctiva (P ≤ .015). Conclusions The usage of the biological adhesive and dissolvent system was applicable for plaque surgery in an ex vivo animal model.

  • erratum to a biological tissue adhesive and dissolvent system for Intraocular Tumor plaque radiotherapy an in vivo animal model experiment
    Graefes Archive for Clinical and Experimental Ophthalmology, 2015
    Co-Authors: Ofira Zloto, Michael Belkin, D Alezra, Oded Sagiv, Vicktoria Vishnevskia Dai, Iris Moroz, Gahl Greenberg, Elad Benartsi, Ido Didi Fabian
    Abstract:

    To examine a novel biological adhesive and dissolvent system for plaque placement and removal using fibrin glue and urokinase, respectively, in an in vivo animal model. The study was performed on 23 rabbit eyes. Of these, eight underwent a technical feasibility study and ultrasonographic plaque displacement measurements, nine were examined clinically and by magnetic resonance imaging and histopathology for tissue reaction to the biological substances used, and in six the impact of fibrin glue as an orbital space occupier on Intraocular pressure was assessed. In an additional ex vivo experiment, the glue's radiation attenuating properties were tested using an oncology EDR2 film. Plaque horizontal movement throughout follow-up (7–10 days) was negligible (0.5 ± 0.2 mm), and there was no tilting whatsoever. In the tissue response experiment, no adverse effects were recorded after application of fibrin or urokinase throughout the 21-day follow-up period. Interestingly, a circumscribed local inflammatory response was noted in tissue surrounding the fibrin glue, and persisted at 21 days. In the orbital space-occupying experiment, application of 1 cc fibrin glue did not cause a significant elevation in Intraocular pressure (IOP) (P = 0.06), and in the ex vivo experiment, there was no significant difference between radiation readings with and without glue separation of the radioactive sources and film (P = 0.065). The adhesive and dissolvent system was feasible and safe for plaque placement and removal. It may be superior to conventional surgical plaque placement methods in eliminating the relatively common risk of plaque tilting and complications due to scleral suturing.